AB0434 EFFICACY AND SAFETY OF OBINUTUZUMAB IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS WITH SECONDARY NON-RESPONSE TO RITUXIMAB.
Authors: J. Arnold, S. Dass, S. Twigg, C. Jones, B. Rhodes, P. Hewins, M. Chakravorty, P. Courtney, M. Ehrenstein, M. Y. Md. Yusof, E. Vital
Journal: Annals of the Rheumatic Diseases (2022)

Background Secondary inefficacy characterized by infusion reactions and anti-drug antibodies occur in 14% of SLE patients treated with repeat rituximab courses(1). Obinutuzumab is a next-generation humanized type-2 anti-CD20 therapy licensed for hematological malignancies which may overcome this issue(2). Objectives We set out to evaluate the clinical efficacy and safety of obinutuzumab in a cohort of rituximab resistant SLE patients. Methods We collated data from SLE patients receiving obinutuzumab for secondary non-response to rituximab in BILAG centres. Disease activity was assessed using BILAG-2004, SLEDAI-2K and serology before, and 6 months after, obinutuzumab 2x1000mg infusions alongside methylprednisolone 100mg. Flow cytometry where possible was carried out using a multiple gating highly sensitive strategy. Results All 9 patients included in the study received obinutuzumab alongside concomitant oral immunosuppression. At 6 months post-obinutuzumab, there were significant reductions in median SLEDAI-2K from 12 to 6 (p=0.014) and total BILAG-2004 score from 21 to 2 (p=0.009). Complement C3 and dsDNA titres improved significantly (both p=0.04). Non statistically significant numerical improvements were seen in C4 levels. Of 8/9 patients receiving concomitant oral prednisolone at baseline (all &gt;10mg/day), 5/9 had their dose reduced at 6 months; 4/8 were on 5mg/day and were in Lupus Low Disease Activity State. After obinutuzumab, 6/9 patients with peripheral B-cell data achieved complete depletion including 4/4 assessed with highly sensitive assays. 1/9 obinutuzumab non-responder required cyclophosphamide therapy. 1 unvaccinated patient died from COVID-19. Table 1. Baseline characteristics, disease activity and steroid doses before and after last obinutuzumab/rituximab. Patient Ethnicity Disease duration (Years) Age (Years) Total BILAG-2004 before Obi Total BILAG-2004 after Obi SLEDAI-2K before Obi SLEDAI-2K after Obi Prednisolone before Obi (mg) Prednisolone after Obi (mg) 1 South Asian 10.8 36.4 18 2 14 8 10 5 2 South Asian 6.3 24.4 24 2 12 4 30 10 3 South Asian 11.9 34.8 29 1 10 4 10 10 4 South Asian 8.2 41.9 21 1 6 0 15 15 5 South Asian 6.8 29.4 32 21 18 14 50 60 6 White European 17.5 37.0 12 8 8 8 15 5 7 White European 16.9 30.0 12 1 12 8 10 5 8 Caribbean 6.2 44.2 25 2 13 0 10 15 9 Caribbean 2.6 21.0 9 2 16 6 10 5 Median (Q1, Q3 ) NA 8.2 (6, 12 ) 34.8 (29,37 ) 21 (12, 25 ) 2 (1, 2 ) 12 (10, 14 ) 6 (4, 8 ) 10 (10, 15 ) 10 (5, 15 ) Conclusion Obinutuzumab appears to be effective and steroid-sparing in renal and non-renal SLE patients with secondary non-response to rituximab. Obinutuzumab was shown to be effective in patients with severe renal and non-renal disease. Therefore, in those with previous responsiveness to B-cell depletion, switching to humanised type-2 anti-CD20 therapy is a logical approach following loss off efficacy. References [1]Vital EM, Dass S, Buch MH, Henshaw K, Pease CT, Martin MF, et al. B cell biomarkers of rituximab responses in systemic lupus erythematosus. Arthritis Rheum [Internet]. 2011 Oct [cited 2020 Oct 12];63(10):3038–47. Available from: https://pubmed.ncbi.nlm.nih.gov/21618204/ [2]Hassan SU, Md Yusof MY, Emery P, Dass S, Vital EM. Biologic Sequencing in Systemic Lupus Erythematosus: After Secondary Non-response to Rituximab, Switching to Humanised Anti-CD20 Agent Is More Effective Than Belimumab. Front Med [Internet]. 2020 Aug 27 [cited 2020 Sep 2];7:498. Available from: https://www.frontiersin.org/article/10.3389/fmed.2020.00498/full Disclosure of Interests Jack Arnold: None declared, Shouvik Dass Consultant of: Roche, Abbvie, UCB &amp; Chugai, Employee of: Honoraria from Roche, Abbvie, UCB &amp; Chugai, Sarah Twigg: None declared, Colin Jones: None declared, Benjamin Rhodes: None declared, Peter Hewins: None declared, Mithun Chakravorty: None declared, Philip Courtney: None declared, Michael Ehrenstein Grant/research support from: GSK, Employee of: Has received honoraria from GSK, Md Yuzaiful Md Yusof: None declared, Edward Vital Employee of: Has received honoraria from Roche